Coenzyme Q10 (CoQ10) was first identified over 70 years ago in an extract from beef heart [1]. As its alternative name ubiquinone suggests, it is widely distributed throughout the body, and is quite highly conserved across mammalian species. CoQ10 has a central role as a redox carrier in the respiratory transport chain, and is found at a high concentration on the inner mitochondrial membrane. Because of this, it is found in the highest concentrations in metabolically active tissues including heart, liver, kidney and pancreas. In addition, it has significant antioxidant properties, inhibiting oxidation of proteins, lipids, and DNA.

Biopsy and autopsy studies have demonstrated a relatively high concentration of CoQ10 in healthy human myocardium, and lower levels in a variety of heart diseases [2, 3]. CoQ10 levels can also be reduced in peripheral blood samples from patients with cardiac problems. With this in mind, CoQ10 has long been postulated as a treatment for heart disease. The first study of CoQ10 as a therapeutic agent in human heart disease was reported in 1967 [4], and further studies have been undertaken since then in a variety of cardiac conditions.

The largest body of evidence relates to the treatment of heart failure. The pathophysiology of heart failure is complex, involving molecular, structural and functional changes. Cardiac metabolism is certainly affected in cardiac failure, and there may be a state of relative energy starvation, so there is some biochemical rationale for hoping that CoQ10 therapy might improve heart failure.

The earliest studies of CoQ10 as a treatment of heart failure were performed on an open label basis, without control groups. Some of these studies suggested very promising results, and provide some data regarding the safety of CoQ10 supplementation, although they must be interpreted with caution due to the methodology.

Quite a number of randomised trials of CoQ10 therapy in heart failure have been performed over the last 30 years or so. Results have been mixed, with some trials demonstrating symptomatic improvement, and some showing small improvements in various investigations including echo and exercise testing [5, 6]. Unfortunately, almost all of these studies have comprised small patient numbers, followed for short periods of time, with very little reporting of important clinical outcomes such as mortality and hospital admission. It is also important to bear in mind that much of the work was undertaken in a previous era of heart failure care, before the widespread use of ACE inhibitors, beta blockers and mineralocorticoid antagonists. The largest randomised, placebo controlled study of CoQ10 treatment in heart failure reported in peer-reviewed literature to date comprises 641 patients followed-up for 1 year, and was published in 1993 [7]. These data show an impressive reduction in hospitalisation for heart failure (37% placebo, 23% CoQ10), but no significant difference in mortality.

A few months ago, the results of a further randomised placebo-controlled trial (Q-SYMBIO) were published [8]. 420 patients were enrolled, and the follow-up period was 2 years. They mostly had NYHA III symptoms, and average LV ejection fraction was 31%. They had fairly good heart failure pharmacotherapy (90% ACE, 74% beta-blocker). With CoQ10 treatment, there was a significant reduction in a combined end-point of cardiac death & heart failure admission (15% vs 26%, p 0.005) and all-cause mortality (10% vs 18%, p 0.036). There were no significant differences between groups in NT pro-BNP level or echocardiographic parameters.

It is now over 10 years since Q-SYMBIO started recruitment, and indeed, the trial had to be stopped early due to slow recruitment. Nonetheless, these data provide by far the strongest evidence to date that CoQ10 therapy may be useful in heart failure. Some questions remain to be answered. In particular, the huge impact on mortality without significant impact on the results of investigations is curious. It is of course possible that much of the benefit of CoQ10 is on other organ systems, and it would be interesting to try and clarify this.

These data are certainly very promising, but it is unlikely that they will lead to the widespread use of CoQ10 at this stage. Other heart failure treatments which are now mainstream therapies were trialled in thousands of patients in multiple studies prior to their introduction into practice guidelines. Another problem is that in most countries, CoQ10 is marketed and regulated as an over-the-counter ‘neutraceutical’ product. Because of this there are a multitude of different formulations and doses available, which may well have differing activities.

Further large scale trials of CoQ10 in heart failure are still required, but it is difficult to see how these will be organised. There is little scope for patenting a product which has been available for such a long time, so there is unlikely to be much interest from mainstream pharmaceutical companies in funding large trials. The global ‘neutraceutical’ industry does have revenue of over $200bn, but these companies may not be keen on the tighter regulations and restrictions which would come with mainstream medical use. We must hope that a public body is able to take on the challenge of organising further large scale studies of CoQ10, and that Q-SYMBIO is a stimulus to a definitive trial of this promising treatment.